Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis.
Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis.
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DOI：
10.3389/fimmu.2021.650491
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发表时间：
2021
影响因子：
7.3
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Gao C;Li H;Liu C;Xu X;Zhuang J;Zhou C;Liu L;Feng F;Sun C
近年来，免疫疗法的出现为三阴性乳腺癌（TNBC）的治疗和管理提供了新的视角。然而，肿瘤突变负荷（TMB）和免疫浸润与TNBC预后之间的关系仍不清楚。本研究为探讨TNBC的免疫原性，根据癌症基因组图谱（TCGA）中TNBC的体细胞突变数据，将TNBC患者分为高、低TMB组，筛选出突变率≥ 10的基因。Kaplan-Meier生存分析显示，高TMB组5年生存率明显高于低TMB组，两组免疫细胞浸润也有差异。进一步探索发现，两组之间表现出显著差异且突变率较高的FAT3基因不仅与TNBC患者的预后显著相关，而且在FAT3基因的野生组和突变组之间表现出免疫细胞浸润的差异。基因集富集分析和药物敏感性分析的结果进一步支持了FAT3基因在TNBC中的重要性。本研究揭示了TMB和免疫细胞浸润在三阴性乳腺癌中的特点及其与预后的关系，为今后TNBC的治疗提供新的生物标志物和潜在的治疗方案。FAT3基因作为TNBC的风险预测基因，被认为是一个潜在的生物学靶点，可能为TNBC的治疗提供新的见解。
In recent years, the emergence of immunotherapy has provided a new perspective for the treatment and management of triple-negative breast cancer (TNBC). However, the relationship between tumor mutation burden (TMB) and immune infiltration and the prognosis of TNBC remains unclear. In this study, to explore the immunogenicity of TNBC, we divided patients with TNBC into high and low TMB groups based on the somatic mutation data of TNBC in The Cancer Genome Atlas (TCGA), and screened out genes with mutation rate ≥10. Then, Kaplan-Meier survival analysis revealed that the 5-year survival rate of the high TMB group was much higher than that of the low TMB group and the two groups also showed differences in immune cell infiltration. Further exploration found that the FAT3 gene, which displays significant difference and a higher mutation rate between the two groups, is not only significantly related to the prognosis of TNBC patients but also exhibits difference in immune cell infiltration between the wild group and the mutant group of the FAT3 gene. The results of gene set enrichment analysis and drug sensitivity analysis further support the importance of the FAT3 gene in TNBC. This study reveals the characteristics of TMB and immune cell infiltration in triple-negative breast cancer and their relationship with prognosis, to provide new biomarkers and potential treatment options for the future treatment of TNBC. The FAT3 gene, as a risk predictor gene of TNBC, is considered a potential biological target and may provide new insight for the treatment of TNBC.